WO1993000863A1 - Procede de fecondation en cycle spontane - Google Patents
Procede de fecondation en cycle spontane Download PDFInfo
- Publication number
- WO1993000863A1 WO1993000863A1 PCT/FR1992/000615 FR9200615W WO9300863A1 WO 1993000863 A1 WO1993000863 A1 WO 1993000863A1 FR 9200615 W FR9200615 W FR 9200615W WO 9300863 A1 WO9300863 A1 WO 9300863A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- oocyte
- fertilization
- container
- puncture
- culture
- Prior art date
Links
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- 230000004720 fertilization Effects 0.000 title claims abstract description 48
- 210000000287 oocyte Anatomy 0.000 claims abstract description 82
- 210000001161 mammalian embryo Anatomy 0.000 claims abstract description 28
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- 238000000338 in vitro Methods 0.000 claims description 14
- 238000002347 injection Methods 0.000 claims description 11
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- 238000012546 transfer Methods 0.000 claims description 11
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- 210000001215 vagina Anatomy 0.000 abstract description 4
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- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 18
- 208000000509 infertility Diseases 0.000 description 12
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- 238000002604 ultrasonography Methods 0.000 description 8
- 208000021267 infertility disease Diseases 0.000 description 7
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 6
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- PYTMYKVIJXPNBD-OQKDUQJOSA-N 2-[4-[(z)-2-chloro-1,2-diphenylethenyl]phenoxy]-n,n-diethylethanamine;hydron;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(/Cl)C1=CC=CC=C1 PYTMYKVIJXPNBD-OQKDUQJOSA-N 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
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- 210000002969 egg yolk Anatomy 0.000 description 1
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- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/42—Gynaecological or obstetrical instruments or methods
- A61B17/425—Gynaecological or obstetrical instruments or methods for reproduction or fertilisation
- A61B17/435—Gynaecological or obstetrical instruments or methods for reproduction or fertilisation for embryo or ova transplantation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/906—Fertility tests
Definitions
- Ovarian stimulation is now conventionally used due to the ease of programming the oocyte retrieval.
- the different ovarian stimulation protocols clomiphene citrate - hMG, hMG alone, FSH - hMG and more recently the LH-RH agonists associated with hMG, have significantly increased the number of oocytes collected during puncture. (from 2.5 to 3.5 on average to 8 to 10 currently). This higher number of oocytes collected had the effect of an increased number of embryos. Due to the risk of multiple pregnancies caused by the transfer of more than three embryos, the majority of assisted procreation centers are equipped with a freezer allowing the embryos to be stored and replaced secondarily. These stimulation protocols due to the quantities of hormones used and the increased number of examinations (hormonal assays and ultrasound examinations) necessary for monitoring follicular growth, are very expensive.
- SEIBEL, MC New techniques in fertilization: Intravaginal culture and microvolume straw. J In Vitro Fert "Embryo Transfer 7": 6, 1990), it reflects the quality of culture and that of gametes.
- a gangue of dense cells of elastic appearance surrounds the embryo which requires its extraction in order to appreciate its stage of development.
- the embryo in the case of mechanical stripping by needle or pipette has never had a stage of development greater than 2 cells, with the presence of fragments and an irregular, asymmetrical and abnormal appearance of the cells.
- the CIV technique is simple, inexpensive, it only requires a small incubator and a stereomicroscope placed under a small laminar flow hood. It does not require any large laboratory infrastructure and in particular a C02 incubator.
- the technique of CIV implies a participation of the patient from where a better psychological context. This technique is more physiological, fertilization being carried out in the vagina at body temperature with the thermal variations normally observed in the periovulatory period. Intravaginal fertilization, raises fewer ethical problems and presents less risk of error between gametes. In addition, there is no risk of incubator failure that could compromise the fertilization of several patients. This technique by its simplicity and its standardization does not require a high level technical training and can be reproduced easily without modification of results.
- the hCG is injected and the oocyte is punctured 34 to 36 hours later. If the diameter is greater than or equal to 18 mm and E2 greater than or equal to 180 mg / ml with the LH between 20 and 40 IU / 1, the hCG is immediately injected and the puncture performed 24 hours after receiving the blood tests . Finally, if the LH is greater than 40 IU / 1, the hCG is not injected and the puncture takes place the day after the assay.
- This simplified protocol made it possible to obtain, in a study of 80 attempts, a pregnancy rate of 22.5% per cycle, of which 17.5% was progressive with the birth of healthy children.
- This protocol offers multiple advantages: monitoring follicular growth is shortened, simple and much less expensive. The puncture of a single follicle is quick, easy and well tolerated by the patient. This technique does not require anesthesia but a simple premedication. Due to the lack of medication, reduced technical time, limited use of single-use instruments, the cost of the procedure is considerably reduced. The absence of stimulation and obtaining a single oocyte does not represent any risk of hyperstimulation. Problems due to embryonic freezing are eliminated. The possibility of multiple pregnancy with the inherent obstetric risk and neonatal morbidity does not exist.
- the subject of the present invention is a fertilization process in which an oocyte puncture is carried out and one or more of these oocytes is introduced into a container containing a culture medium, without interposition of air. or C0 2 , intended for fertilization and culture of oocyte (s), as well as sperm, and the container, once closed, is introduced into the vaginal cavity or into the uterus in order to allow fertilization of the oocyte (s) and culture of the embryo (s), characterized in that it is carried out without stimulation of the cycle with monitoring of LH by blood assays and the programming of the oocyte puncture according to the value of LH.
- the puncture is scheduled 34 to 36 hours after a doubling of the value of the base LH with a rate lower than 40 IU / 1.
- the oocyte retrieval is programmed at approximately 48 hours after having detected the doubling of the basic value.
- the maturation of the oocyte (s) is carried out after collection. This maturation is preferably carried out by maintaining the container at a temperature of approximately 37 "for 2 to 6 hours.
- the method can be implemented with a single punctured and fertilized oocyte.
- a kit which includes a rapid LH dosing device, an oocyte puncture needle, a filtration unit for semen preparation, a container for fertilization or for oocytes and culture. of the embryo (s) with its submerged means of restraint. Culture media can be added for rinsing the follicle, preparing sperm, maturing and fertilizing the oocyte.
- the kit can also include a disposable speculum, a catheter for transferring the embryo (s) and / or an hCG injection syringe.
- a method of fertilization of oocyte (s) in vitro and culture of embryo (s) in which the following steps are carried out in the absence of air enriched with C0 2 filling of a container of a liquid culture medium for oocyte and embryo and at least one oocyte and sperm, closing the container, introduction of the container into the vaginal cavity or into the uterus in order to obtain fertilization and cleavage of the or fertilized oocytes, characterized in that before the introduction of the container into the vaginal cavity or into the uterus it is kept at a temperature of about 37 ° for 2 to 6 hours.
- GROUP 1 (from August 1990 to February 1991), 15 patients were included in this group, 11 under 40 and 4 whose age exceeded 40. 25 attempts, by this IVF procedure in the office were carried out . 3 patients in fact benefited from 3 procedures, 4 from 2 procedures. The indications for which IVF was decided, were for 9 of these patients a factor of tubal sterility, for 3 of them a factor of sterility of male origin, in 1 case an unexplained sterility and finally in 2 cases a cervical factor . What characterizes this group 1 and which fundamentally differentiates it from group 2, is the supplementation of the luteal phase. In this group, this supplementation was synthetic progesterone injected intramuscularly every day, at a dose of 25 or 50 mg.
- GROUP 2 (from March 1991 to May 1991), 16 patients were included in this group. Each having benefited from an attempt, ie 16 attempts. 13 attempts were made in patients under 40 years of age, 3 in patients over 40 years of age. In 9 cases sterility was of tubal origin, in 4 of unexplained origin, in 2 endometriosis was responsible, in the last case a male factor.
- the luteal phase supplementation was performed using hCG as initially during our spontaneous cycle study. The intramuscular injection of hCG was performed on the day of the transfer 1500 IU / 1, and repeated 2 other times three days apart.
- GROUP 1 Of the 25 attempts, 18 resulted in Obtaining oocytes with in 4 attempts obtaining 2 oocytes. Of these 22 oocytes, 22 embryos were obtained after CIV, but only 2 biochemical pregnancies resulted from the transfer of these embryos. Of the 7 attempts without oocytes, 5 were due to a torn or ruptured follicle during the puncture, 1 for an ovulation before puncture, in the last oocyte was not obtained after several rinses. GROUP 2. Of the 16 attempts, 16 oocytes were obtained but 2 of them presented a ruptured pellucid zone, and therefore only 14 embryos resulted from IVC fertilization.
- the puncture was then scheduled 34 to 36 hours after the blood sample, the next day in the evening.
- a blood sample was then systematically taken in the afternoon (3 to 5 hours) sometimes revealing a stagnation of LH, with an LH value almost identical to that of the morning and always less than 40 IU / I .
- Analysis of these first results and the absence of pregnancy in this type of stagnation suggests that the puncture was performed too early.
- the puncture must be postponed until the next day for better oocyte maturation. With the exception of patients over 40 years of age, due to the major risk of ovulation before puncture, oocyte maturation seems to take place more quickly.
- the LH value of the next dosage (generally the next morning) reveals an LH value greater than 40 IU / 1 thus confirming the stagnation of the previous dosage.
- the puncture must be programmed as expected 34 to 36 hours after the first doubling of the LH.
- the puncture will be programmed as soon as three dosages of E2 give the same value after doubling the base value of LH. If the level of E2 the day after the presumed LH surge has increased by more than 20% above the rate of doubling compared to the base value, the puncture will be performed 30 to 34 hours after reaching the higher level of E2 (early false LH peak).
- Another peculiarity was to inject the 5000 IU of hCG immediately after the oocyte retrieval, supplementation of the luteal phase by hCG taking place as previously described.
- a maturation phase was added after the oocyte collection.
- the oocyte is placed at 37 ° C for 2 to 30 hours in a tube completely filled with culture medium (B2 from Menezo) without the interposition of air and C02.
- the essential element for programming the puncture seems to be to monitor the evolution of blood LH. Programming the oocyte puncture on the results of 2 daily LH blood tests may seem imprecise and ineffective. However, the results obtained on the first 8 attempts demonstrate the opposite, both by the number of oocytes collected (8/8) and by the number of embryos obtained (8/8). This new protocol on two blood assays of E2 on the same day appears to give equivalent results superior to those of the puncture on injection of hCG.
- the essential element lies in obtaining an LH dosage above 40 UT / 1. Obtaining such a rate will lead to the puncture 24 hours after the blood sample, and possibly to delay the time of a puncture whose programming had been decided on Your first LH dosages.
- Small equipment used punctcture needle, syringes, petri dishes, tubes for semen preparation, tube or container for CIV with its embedded compression method (possibly plastic speculum, compresses, plastic forceps, sterile bag to cover the vaginal probe) and medium culture for rinsing the follicle, for washing the sperm, for maturation and fertilization of the oocyte (all these instruments being sterilized with gamma rays and individually wrapped in cellophane pouch) is a single-use material.
- the selection of this type of equipment requires a lot of attention and experience, in order to avoid any toxicity and to obtain the most suitable equipment for this type of procedure.
- kits To the small equipment previously mentioned could be added the filtration unit for sperm preparation that I developed and a rapid LH dosing device known per se, as well as the hCG ampoules used to supplement the luteal phase .
- the kit will therefore include a rapid LH dosing device, an oocyte puncture needle (s), a container for maturing oocytes using the CIV technique and a container for fertilization of the same oocytes or possibly a container for maturation and fertilization of oocytes.
- a rapid LH dosing device an oocyte puncture needle (s)
- s oocyte puncture needle
- container for maturing oocytes using the CIV technique a container for fertilization of the same oocytes or possibly a container for maturation and fertilization of oocytes.
- WO 88/08280 filed on May 2, 1988 the container can be at least partially biodegradable, the content of this request being incorporated into the present request by simple reference.
- the kit would represent a considerable time and energy saving for the practitioner using this type of procedure, it would be the guarantee of a procedure carried out in the best conditions.
- This natural cycle can also be combined with the flake fertilization technique that we have already developed. Extreme simplification of IVF will occur with biodegradable glitter. The procedure will therefore not require embryo transfer and the only human technical intervention will aim to prepare and associate the 2 gametes (oocyte and sperm) for fertilization actually carried out in vivo.
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- Health & Medical Sciences (AREA)
- Surgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- Reproductive Health (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Fertilizing (AREA)
- Fats And Perfumes (AREA)
- Catching Or Destruction (AREA)
- Detergent Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fertilizers (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP92914635A EP0546155B1 (fr) | 1991-07-01 | 1992-07-01 | Procede de fecondation en cycle spontane |
| DE69229259T DE69229259D1 (de) | 1991-07-01 | 1992-07-01 | Befruchtungsverfahren bei einem von selbst ablaufenden zyklus |
| US07/977,409 US5532155A (en) | 1991-07-01 | 1992-07-01 | Spontaneous cycle fertilization method |
| CA002090721A CA2090721C (fr) | 1991-07-01 | 1992-07-01 | Procede de fecondation en cycle spontane |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR91/08177 | 1991-07-01 | ||
| FR9108177A FR2678506B1 (fr) | 1991-07-01 | 1991-07-01 | Procede de fecondation en cycle spontane. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1993000863A1 true WO1993000863A1 (fr) | 1993-01-21 |
Family
ID=9414546
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/FR1992/000615 WO1993000863A1 (fr) | 1991-07-01 | 1992-07-01 | Procede de fecondation en cycle spontane |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5532155A (ru) |
| EP (1) | EP0546155B1 (ru) |
| AT (1) | ATE180401T1 (ru) |
| AU (1) | AU2278692A (ru) |
| CA (1) | CA2090721C (ru) |
| DE (1) | DE69229259D1 (ru) |
| FR (1) | FR2678506B1 (ru) |
| RU (1) | RU2152758C2 (ru) |
| WO (1) | WO1993000863A1 (ru) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2276322A (en) * | 1993-03-24 | 1994-09-28 | Rudiger Ulrich Josef Pitroff | Mammalian embryo fertilization and incubation device |
| WO2004035766A2 (en) * | 2002-10-15 | 2004-04-29 | Novo Nordisk A/S | In vitro synchronisation of nuclear and cytoplasmatic maturation of oocytes involving addition and removal of phosphodiesterase type 3 inhibitor |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1562035B1 (en) | 1997-01-31 | 2017-01-25 | Xy, Llc | Optical apparatus and method |
| US6149867A (en) | 1997-12-31 | 2000-11-21 | Xy, Inc. | Sheath fluids and collection systems for sex-specific cytometer sorting of sperm |
| JP2002521043A (ja) | 1998-07-30 | 2002-07-16 | エックスワイ，インコーポレイテッド | 非外科的人工授精のためのウマシステム |
| US7208265B1 (en) | 1999-11-24 | 2007-04-24 | Xy, Inc. | Method of cryopreserving selected sperm cells |
| NZ551401A (en) | 2000-05-09 | 2009-12-24 | Xy Inc | A particle differentiation apparatus which differentiates between X-chromosome bearing and Y-chromosome bearing populations of spermatozoa |
| US7713687B2 (en) | 2000-11-29 | 2010-05-11 | Xy, Inc. | System to separate frozen-thawed spermatozoa into x-chromosome bearing and y-chromosome bearing populations |
| AU2002220018A1 (en) | 2000-11-29 | 2002-06-11 | Colorado State University | System for in-vitro fertilization with spermatozoa separated into x-chromosome and y-chromosome bearing populations |
| WO2003086251A1 (fr) * | 2002-04-17 | 2003-10-23 | Yuriy Vladimirovich Komissarov | Procede de conception d'enfants 'selection naturelle' et procede correspondant |
| US8486618B2 (en) | 2002-08-01 | 2013-07-16 | Xy, Llc | Heterogeneous inseminate system |
| CA2532376C (en) | 2002-08-01 | 2015-05-12 | Colorado State University Research Foundation | Low pressure sperm cell separation system |
| BRPI0313476B1 (pt) | 2002-08-15 | 2015-06-23 | Xy Llc | Citômetro de fluxo de alta resolução |
| US7169548B2 (en) | 2002-09-13 | 2007-01-30 | Xy, Inc. | Sperm cell processing and preservation systems |
| MX345105B (es) | 2003-03-28 | 2017-01-16 | Inguran Llc * | Método de fotodaño para separar partículas. |
| AU2004242121B2 (en) | 2003-05-15 | 2010-06-24 | Xy, Llc. | Efficient haploid cell sorting for flow cytometer systems |
| AU2005228893B2 (en) | 2004-03-29 | 2010-08-19 | Inguran, Llc | Sperm suspensions for sorting into X or Y chromosome-bearing enriched populations |
| EP1765983A4 (en) | 2004-05-17 | 2008-10-22 | Gen Hospital Corp | METHODS AND COMPOSITIONS FOR THE PRODUCTION OF STEM CELLS FROM GERMINAL STEM CELLS DERIVED FROM SPINAL CORD |
| JP2008507287A (ja) | 2004-07-22 | 2008-03-13 | モンサント テクノロジー エルエルシー | 精子細胞の集団を富化する方法 |
| CN103562378B (zh) | 2011-04-14 | 2016-09-07 | 通用医疗公司 | 用于自体种系线粒体能量转移的组合物和方法 |
| EP3495470A1 (en) | 2011-06-29 | 2019-06-12 | The General Hospital Corporation | In vivo methods for enhancing bioenergetic status in female germ cells |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4010738A (en) * | 1974-10-30 | 1977-03-08 | The Trustees Of The University Of Pennsylvania | Method of predicting and detecting ovulation |
| EP0131166A1 (en) * | 1983-06-14 | 1985-01-16 | Fertility And Genetics Research, Inc. | Non-surgical apparatus for human embryo transfer |
| EP0153190A1 (en) * | 1984-02-20 | 1985-08-28 | Olympus Optical Co., Ltd. | Endoscopic ovum picker instruments |
| WO1988008280A1 (fr) | 1987-04-30 | 1988-11-03 | Claude Ranoux | Procede de fecondation intra-uterine de mammifere et dispositif pour sa mise en oeuvre |
| FR2614899A1 (fr) * | 1987-05-07 | 1988-11-10 | Ranoux Claude | Dispositif pour preparation selection et capacitation des spermatozoides humains et animaux par filtration |
-
1991
- 1991-07-01 FR FR9108177A patent/FR2678506B1/fr not_active Expired - Fee Related
-
1992
- 1992-07-01 DE DE69229259T patent/DE69229259D1/de not_active Expired - Lifetime
- 1992-07-01 EP EP92914635A patent/EP0546155B1/fr not_active Expired - Lifetime
- 1992-07-01 AU AU22786/92A patent/AU2278692A/en not_active Abandoned
- 1992-07-01 WO PCT/FR1992/000615 patent/WO1993000863A1/fr active IP Right Grant
- 1992-07-01 US US07/977,409 patent/US5532155A/en not_active Expired - Lifetime
- 1992-07-01 CA CA002090721A patent/CA2090721C/fr not_active Expired - Fee Related
- 1992-07-01 RU RU93005171/14A patent/RU2152758C2/ru not_active IP Right Cessation
- 1992-07-01 AT AT92914635T patent/ATE180401T1/de not_active IP Right Cessation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4010738A (en) * | 1974-10-30 | 1977-03-08 | The Trustees Of The University Of Pennsylvania | Method of predicting and detecting ovulation |
| EP0131166A1 (en) * | 1983-06-14 | 1985-01-16 | Fertility And Genetics Research, Inc. | Non-surgical apparatus for human embryo transfer |
| EP0153190A1 (en) * | 1984-02-20 | 1985-08-28 | Olympus Optical Co., Ltd. | Endoscopic ovum picker instruments |
| WO1988008280A1 (fr) | 1987-04-30 | 1988-11-03 | Claude Ranoux | Procede de fecondation intra-uterine de mammifere et dispositif pour sa mise en oeuvre |
| FR2614899A1 (fr) * | 1987-05-07 | 1988-11-10 | Ranoux Claude | Dispositif pour preparation selection et capacitation des spermatozoides humains et animaux par filtration |
Non-Patent Citations (1)
| Title |
|---|
| FERTILITY AND STERILITY vol. 52, no. 4, Octobre 1989, pages 617 - 621 FOULOT ET AL. 'In vitro fertilization without ovarian stimulation: a simplified protocol applied in 80 cycles' cité dans la demande * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2276322A (en) * | 1993-03-24 | 1994-09-28 | Rudiger Ulrich Josef Pitroff | Mammalian embryo fertilization and incubation device |
| WO2004035766A2 (en) * | 2002-10-15 | 2004-04-29 | Novo Nordisk A/S | In vitro synchronisation of nuclear and cytoplasmatic maturation of oocytes involving addition and removal of phosphodiesterase type 3 inhibitor |
| WO2004035766A3 (en) * | 2002-10-15 | 2004-06-03 | Novo Nordisk As | In vitro synchronisation of nuclear and cytoplasmatic maturation of oocytes involving addition and removal of phosphodiesterase type 3 inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2278692A (en) | 1993-02-11 |
| ATE180401T1 (de) | 1999-06-15 |
| CA2090721C (fr) | 2004-06-29 |
| EP0546155A1 (fr) | 1993-06-16 |
| FR2678506A1 (fr) | 1993-01-08 |
| DE69229259D1 (de) | 1999-07-01 |
| EP0546155B1 (fr) | 1999-05-26 |
| FR2678506B1 (fr) | 2000-03-10 |
| US5532155A (en) | 1996-07-02 |
| RU2152758C2 (ru) | 2000-07-20 |
| CA2090721A1 (fr) | 1993-01-02 |
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